Power Doppler and spectral Doppler measurements of knee-joint synovitis in rheumatoid arthritis patients with superficial pattern signals and in those with deep pattern signals

Power Doppler and spectral Doppler ultrasonography were used to scan 127 knee joints of 72 patients with rheumatoid arthritis (RA). Synovial effusion thickness and synovial proliferation (pannus) thickness, as well as the flow signal diameter, were measured on ultrasonogram prints of the power Doppler using digital calipers. In addition, color-flow signal grades on power Doppler and the resistance index (RI) values on spectral Doppler were evaluated. The values of these five variables were compared among 58 joints with superficial pattern flow signals and 69 joints with deep pattern flow signals. Compared with the joints with deep pattern signals, the joints with superficial pattern signals had significantly higher mean values of effusion thickness (P < 0.0001) and flow signal grades (P < 0.0001), and significantly lower mean RI (P < 0.0001). On the other hand, the joints with deep pattern signals had a significantly higher value of signal diameter (P = 0.0125) and had a trend to higher value of pannus thickness (P = 0.079) as well. Significant correlations were observed between effusion thickness and signal grades (P < 0.0001); effusion thickness and RI (P < 0.0001); signal diameter and pannus thickness (P = 0.0102); signal diameter and RI (P < 0.0001); and signal grades and RI (P < 0.0001). The ultrasonographic measurements of synovitis in RA patients provide valuable information on synovial inflammation.     

Comparison in values of color flow signals and vascular resistance of synovial vascularity demonstrated by Doppler sonography between knee and metacarpophalangeal joints of patients with rheumatoid arthritis

Synovial vascularity of 12 patients with rheumatoid arthritis (RA) was examined by Doppler sonography for color flow signals and vascular resistance on knee joints and metacarpophalangeal (MCP) joints, and the results were compared with each other and with C-reactive protein (CRP) levels of the patients. A significant correlation was observed between knee resistance index (RI) and MCP-RI (P = 0.0140), but not between knee color flow signals and MCP color flow signals (P = 0.1029). A significant correlation was also observed between knee color flow signals and knee RI (P = 0.0107), and knee pulsatility index (PI) (P = 0.0146). On the other hand, no correlation was observed between MCP color flow signals and MCP-RI (P = 0.828), and MCP-PI (P = 0.434). There was no significant correlation between CRP levels and grades of color flow signals, RI, and PI for both knee and MCP joints. Doppler sonographic evaluation of RI, especially knee RI, could be a useful marker for estimating synovial inflammation in RA patients.     

Comparison in values of color flow signals and vascular resistance of synovial vascularity demonstrated by Doppler sonography between knee and metacarpophalangeal joints of patients with rheumatoid arthritis

Abstract

Synovial vascularity of 12 patients with rheumatoid arthritis (RA) was examined by Doppler sonography for color flow signals and vascular resistance on knee joints and metacarpophalangeal (MCP) joints, and the results were compared with each other and with C-reactive protein (CRP) levels of the patients. A significant correlation was observed between knee resistance index (RI) and MCP-RI (P = 0.0140), but not between knee color flow signals and MCP color flow signals (P = 0.1029). A significant correlation was also observed between knee color flow signals and knee RI (P = 0.0107), and knee pulsatility index (PI) (P = 0.0146). On the other hand, no correlation was observed between MCP color flow signals and MCP-RI (P = 0.828), and MCP-PI (P = 0.434). There was no significant correlation between CRP levels and grades of color flow signals, RI, and PI for both knee and MCP joints. Doppler sonographic evaluation of RI, especially knee RI, could be a useful marker for estimating synovial inflammation in RA patients.     

Doppler sonographic comparative study on usefulness of synovial vascularity between knee and metacarpophalangeal joints for evaluation of articular inflammation in patients with rheumatoid arthritis treated by infliximab

We used Doppler sonography to evaluate the therapeutic effects of infliximab on the knee and metacarpophalangeal (MCP) joints of 10 patients with rheumatoid arthritis (RA), based on the color flow signals (CFS) and resistance index (RI) of synovial vascularity. After three injections of infliximab, we observed significant improvement in numbers of tender joints (P < 0.01), values of C-reactive protein (CRP) (P < 0.01), erythrocyte sedimentation rate (ESR) (P < 0.001), disease activity scores including tender joints, swollen joints, and ESR (DAS28-E3) (P < 0.0001), and CFS of knee (P < 0.001) and MCP (P < 0.05) joints. There was no significant improvement in RI values of knee or MCP joints after the therapy. We observed significant correlation between CFS of knee joints (knee-CFS) and values of CRP (P < 0.01), ESR (P < 0.01), and DAS28-E3 (P < 0.05), but not between CFS of MCP joints (MCP-CFS) and values of CRP, ESR, and DAS28-E3. However, no significant correlation was observed between 10 difference values (before values–after values) of CFS grades of knee or MCP joints and 10 difference values each of CRP, ESR, or DAS28-E3. The knee joints are more suitable than MCP joints for obtaining CFS in Doppler sonography, and are more useful than MCP joints for evaluation.     

Doppler sonographic comparative study on usefulness of synovial vascularity between knee and metacarpophalangeal joints for evaluation of articular inflammation in patients with rheumatoid arthritis treated by infliximab

Abstract

We used Doppler sonography to evaluate the therapeutic effects of infliximab on the knee and metacarpophalangeal (MCP) joints of 10 patients with rheumatoid arthritis (RA), based on the color flow signals (CFS) and resistance index (RI) of synovial vascularity. After three injections of infliximab, we observed significant improvement in numbers of tender joints (P < 0.01), values of C-reactive protein (CRP) (P < 0.01), erythrocyte sedimentation rate (ESR) (P < 0.001), disease activity scores including tender joints, swollen joints, and ESR (DAS28-E3) (P < 0.0001), and CFS of knee (P < 0.001) and MCP (P < 0.05) joints. There was no significant improvement in RI values of knee or MCP joints after the therapy. We observed significant correlation between CFS of knee joints (knee-CFS) and values of CRP (P < 0.01), ESR (P < 0.01), and DAS28-E3 (P < 0.05), but not between CFS of MCP joints (MCP-CFS) and values of CRP, ESR, and DAS28-E3. However, no significant correlation was observed between 10 difference values (before values–after values) of CFS grades of knee or MCP joints and 10 difference values each of CRP, ESR, or DAS28-E3. The knee joints are more suitable than MCP joints for obtaining CFS in Doppler sonography, and are more useful than MCP joints for evaluation.     

Evaluation of pannus and vascularization of the metacarpophalangeal and proximal interphalangeal joints in rheumatoid arthritis by high-resolution ultrasound (multidimensional linear array).

OBJECTIVE: To evaluate the extent of intraarticular vascularization and pannus formation in metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of patients with rheumatoid arthritis (RA) by high-resolution ultrasound (US). METHODS: A newly developed, high-resolution multidimensional linear array US was utilized to obtain longitudinal and transverse scans of joints with active RA (n = 21), moderately active RA (n = 39), or inactive RA (n = 93), and of joints from healthy controls (n = 120). RESULTS: Healthy joints had no detectable pannus, whereas pannus could be detected in 52% of the joints with active RA, 82% of the joints with moderately active RA, and 67% of the joints with inactive RA. There was a significant difference in vascularization in the joints of all subgroups of RA patients and those of healthy subjects (P < 0.001). Moreover, vascularization differed significantly among the RA subgroups: inactive versus moderately active RA (P < 0.02) and inactive versus active RA (P < 0.05). Both pannus and vascularization appeared to be localized preferentially on the radial side of the joints. CONCLUSION: Evaluation of pannus and the extent of vascularization within the joints of patients with RA by high-resolution US might be helpful in the assessment of disease activity, and thus influence therapeutic strategies.     

Comparison of ultrasonographic assessment of synovitis and joint vascularity with radiographic evaluation in a randomized, placebo-controlled study of infliximab therapy in early rheumatoid arthritis

OBJECTIVE: To investigate sensitive ultrasonographic imaging methods for detection of synovial thickness and vascularity to discriminate between patients with early rheumatoid arthritis (RA) receiving infliximab + methotrexate (MTX) versus placebo + MTX over 18 weeks, and to compare the relationship between synovial thickening and vascularity at baseline and radiologic damage to joints of the hands and feet at 54 weeks. METHODS: Patients with early RA (duration <3 years) receiving stable dosages of MTX were randomly assigned to receive blinded infusions of 5 mg/kg infliximab (n = 12) or placebo (n = 12) at weeks 0, 2, 6, and then every 8 weeks until week 46. At baseline and week 18, clinical assessments were performed, and metacarpophalangeal joints were assessed by high-frequency ultrasonography and power Doppler ultrasonography measurements. Radiographs of the hands and feet taken at baseline and at 54 weeks were evaluated using the van der Heijde modification of the Sharp method (vdH-Sharp score). RESULTS: Using changes in the total vdH-Sharp score over 54 weeks and changes in synovial thickening and joint vascularity at 18 weeks, we were able to distinguish those patients receiving infusions of infliximab + MTX from those receiving placebo + MTX. Sonographic measurements of synovial thickening and vascularity at baseline in the placebo + MTX group demonstrated clear relationships with the magnitude of radiologic joint damage at week 54. Infliximab + MTX treatment abolished these relationships. CONCLUSION: The delay or reversal of inflammatory and joint-destructive mechanisms in patients with early RA was already apparent following 18 weeks of treatment with infliximab + MTX and was reflected in radiologic changes at 54 weeks.     

Involvement of fibroblast growth factor-2 in joint destruction of rheumatoid arthritis patients.

OBJECTIVE: To investigate the effect of the synovial fluid from knee joints of rheumatoid arthritis (RA) patients with different severities of joint destruction on osteoclastogenesis and bone resorption. METHODS: Synovial fluid was harvested from the knee joints of 59 RA patients and 37 ostcoarthritis (OA) patients. RA patients with Larsen's knee grade 1-3 were classified as mild RA (n = 30) and those with grade 4 or 5 as severe RA (n = 29). Cytokine concentrations in synovial fluid were measured by ELISA. Osteoclastogenesis was measured by tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cell (MNC) formation in a co-culture of mouse osteoblastic cells and bone marrow cells, and bone resorption by 45Ca release from pre-labelled cultured neonatal mouse calvariae. RESULTS: The synovial fluid of severe RA patients significantly stimulated TRAP-positive MNC formation and 45Ca release compared to those of mild RA and OA patients. Among the bone-resorptive cytokines fibroblast growth factor-2 (FGF-2), tumour necrosis factor alpha (TNF-alpha), interleukin-1alpha (IL-1alpha), IL-6 and soluble IL-6 receptor (sIL-6R), only FGF-2 concentration in the synovial fluid was positively correlated to Larsen's grade, and severe RA patients showed significantly higher FGF-2 concentrations than mild RA patients. Osteoclastogenesis in a co-culture system which was stimulated by the synovial fluid of severe RA patients was significantly inhibited by a neutralizing antibody against FGF-2 and this inhibition was stronger than antibodies against other cytokines. CONCLUSION: The increase in endogenous FGF-2 levels in the synovial fluid of RA patients may play a role in the joint destruction by inducing osteoclastogenesis.     

Power Doppler sonography in the assessment of synovial tissue of the knee joint in rheumatoid arthritis: a preliminary experience

OBJECTIVE: To investigate the intra-articular vascularisation of the synovial pannus in the knee of patients with rheumatoid arthritis (RA) with power Doppler ultrasonography (PDS) and an echo contrast agent and correlate the area under the time-intensity curves with the clinical findings and laboratory measures of disease activity. METHOD: Forty two patients with RA (31 women, 11 men) with history and signs of knee arthritis, classified according to a modified index of synovitis activity (active, moderately active, and inactive), were studied. Clinical and functional assessment (number of swollen joints, intensity of pain, general health-visual analogue scale, disability index-Health Assessment Questionnaire, Ritchie articular index) and a laboratory evaluation were made on all patients. Disease activity was evaluated using the disease activity score (DAS) and the chronic arthritis systemic index (CASI) for each patient. All patients were examined with conventional ultrasonography and PDS before injection of intravenous ultrasound contrast agent (Levovist). The quantitative estimation of the vascularisation of the synovial membrane was performed with time-intensity curves and calculation of the area under the curves. RESULTS: The mean (SD) value of the area underlying time-intensity curves was 216.2 (33.4) in patients with active synovitis, 186.8 (25.8) in patients with moderately active synovitis, and 169.6 (20.6) in those with inactive synovitis. The mean value of the areas differed significantly between the patients with active and those with inactive synovitis (p<0.01). The mean value of the area under the curve of the entire group was weakly correlated with the number of swollen joints (p=0.038), but a strong correlation was found with composite indexes of disease activity such as the DAS (p=0.006) and CASI (p=0.01). No correlation was found with age, disease duration, and other laboratory and clinical variables. CONCLUSION: PDS may be a valuable tool to detect fractional vascular volume and to assist clinicians in distinguishing between inflammatory and non-inflammatory pannus. The transit of microbubbles of ultrasound contrast across a tissue can be used to estimate haemodynamic alterations and may have a role in assessing synovial activity and the therapeutic response to treatment of synovitis of the knee joint.     

Clinical aspects of involutional osteoporosis

Abstract

Based on findings which suggested the involvement of the neuropeptide substance P in the pathogenesis of rheumatoid arthritis (RA), we investigated the mechanism of synovial pannus formation in RA, and examined the interaction between the cytokine production of synovial tissues and the concentration of substance P in the cartilage–pannus junction (CPJ). The CPJ and other peripheral synovial tissues were separately obtained from each part of the synovium from the knee joints of seven RA patients. The concentrations of substance P and the cytokines interleukin (IL)-1β and IL-6 in the CPJ and peripheral synovial tissues were determined by enzyme-linked immunosorbent assays. In addition, synovial cells were isolated from the CPJ and peripheral synovial tissues and treated with substance P or neurokinin-1 receptor antagonist to analyze the changes in cytokine production. The substance P levels were 211.2 and 50.5 pg/mg protein in the CPJ and the peripheral synovium, respectively. The IL-1β and IL-6 levels in the CPJ were 24.6 and 12.8 pg/mg protein, respectively. In the peripheral synovium, these levels were 4.3 and 2.5 pg/mg protein, respectively. In the CPJ, the IL-1β and IL-6 levels in tissue containing a high concentration of substance P (>200 pg/mg protein) were 39.4 and 21.6 pg/mg protein, respectively, and those in tissue containing a low concentration of substance P (≤200 pg/mg protein) were 11.6 and 5.1 pg/mg protein, respectively. Synovial cells from the CPJ produced higher levels of IL-1β and IL-6 than those from peripheral tissues. In addition, treatment of the cells with an NK-1 antagonist significantly reduced the production of these cytokines by the synovial cells. The theory that substance P plays a role in the pathogenesis of RA via the upregulation of cytokine production should be considered in further studies on the immunomodulatory properties of substance P in arthritis.     

A comparison of clinical vs ultrasound determined synovitis in rheumatoid arthritis utilizing gray-scale, power Doppler and the intravenous microbubble contrast agent 'Sono-Vue'

OBJECTIVES: Synovitis in rheumatoid arthritis (RA) is assessed clinically by the presence of joint tenderness and swelling. Synovial thickening and increased vascularity may also be detected by high-resolution ultrasonography (US) and power Doppler (PD). This study investigated the relationship between clinical and sonographic features of synovial disease utilizing US, PD and the contrast agent Sono-Vue. METHODS: Forty RA patients were recruited. One proximal inter-phalangeal or metacarpophalangeal joint was selected per patient, as being unambiguously either: swollen and tender, just swollen, just tender or neither swollen nor tender (Nil). Ten joints were selected per clinical group. On US, the mean synovial thickness was measured and synovial hypertrophy and erosions were graded subjectively. Synovial vascularity demonstrated by PD was scored subjectively pre- and post-contrast. RESULTS: All grades of synovial vascularity were found in each clinical group including the Nil group. There were significant differences between the four clinical groups for both synovial hypertrophy (P = 0.024) and PD scores pre- (P = 0.022) and post- (P = 0.039) contrast. Tender-only joints showed significantly less vascularity than other groups. Post-contrast, the median PD scores increased in all but the Nil group, in some cases from the normal to abnormal range. CONCLUSION: Synovitis demonstrated by US and PD is not predicted by patterns of disease as described by joint swelling and tenderness despite unambiguous selection of joints. Synovial vascularity was the least in tender-only joints and was heterogeneous in all other groups, including Nil joints. These findings question the reliability of traditional clinical signs in RA synovitis assessment.     

Detritus synovitis in chronic polyarthritis: a clinical and operation histologic evaluation

In rheumatoid arthritis (RA) joint inflammation is due to two processes: 1) the underlying inflammatory process (UIP) characterized by a lymphoplasmacellular infiltration of the synovial tissue, as well as pannus formation, and 2) the detritogenic synovitis (DS), a synovial response to articular wear products from cartilage and bone (detritus) that induces a preferentially fibrinous inflammation. In order to estimate the role of DS in the clinical presentation of such joints, 40 patients with RA undergoing knee-joint surgery on 48 occasions were evaluated for clinical parameters, radiological stage (Larsen), and histopathological characteristics of UIP and DS. The clinical parameters were comparable in knee joints with predominantly UIP or DS. However, DS was regularly seen in knees with advanced destruction according to Larsen's stages 4 to 5, while UIP occurres in joints even without radiological damage. In conclusion, it is assumed that the poor response of patients with advanced RA to so-called long-term drug therapy may be in part explained by the modifying influence of joint detritus on the underlying "rheumatoid" inflammatory process.     

Ultrasonographic and radiographic results from a two-year controlled trial of immediate or one-year-delayed addition of infliximab to ongoing methotrexate therapy in patients with erosive early rheumatoid arthritis

OBJECTIVE: To compare the impact of immediate and delayed introduction of anti-tumor necrosis factor therapy on inflammation and structural damage in methotrexate (MTX)-treated patients with early rheumatoid arthritis (RA). METHODS: Twenty-four patients with erosive early RA (duration < 3 years) who were receiving MTX were randomized to receive infliximab 5 mg/kg or placebo infusions at weeks 0, 2, and 6, and then every 8 weeks through week 46. Beginning at week 54 and thereafter, all patients received infliximab 5 mg/kg. Metacarpophalangeal joints were scanned using high-frequency ultrasonography and power Doppler imaging. Radiographs were evaluated using the modified Sharp/van der Heijde scoring system. RESULTS: From baseline to week 54, total synovial thickness was significantly improved in the infliximab + MTX group compared with the placebo + MTX group (median reduction 95.8% versus 37.5%; P = 0.005), as was the total color Doppler area (CDA; vascularity assessment) (median reduction 100% and 47.1%, respectively; P = 0.025). From week 0 to week 110, no significant between-group difference was observed in the change from baseline for total synovial thickening or the total CDA. At week 54, greater progression in the Sharp/van der Heijde score was apparent in patients receiving placebo + MTX compared with those receiving infliximab + MTX. Although radiographic progression in the placebo + MTX group was greatly reduced in the second year (after initiation of infliximab therapy), marked differences were observed between the infliximab + MTX group (median change in the Sharp/van der Heijde score 4.0) and the placebo + MTX group (median change 14.5) from baseline to week 110 (P = 0.076). CONCLUSION: The results indicate that the efficacy of 2 years of combination therapy with infliximab + MTX for inhibiting cumulative structural damage was superior to that of 1 year of treatment with MTX alone followed by the addition of infliximab.     

Assessment of inflamed synovial membrane in the knee joint by dynamic magnetic resonance imaging

Abstract

Dynamic magnetic resonance imaging (dynamic MRI) was used to examine the synovial membrane in the knee joints of 15 patients with rheumatoid arthritis (RA) in order to investigate the relationship between pathological and MRI findings. Signal intensities in the regions of interest (ROI), identified as the synovial membrane of the suprapatellar pouch, were measured on MR images. Signal intensities at various times after the injection of contrast medium Gd–diethylenetriaminopentoacetic acid (Gd–DTPA) were normalized relative to the signal intensity at 80?s, and designated as the normalized signal intensity (NSI). Pathological findings were quantified, and the types of inflamed synovial membrane were classified as either acute or chronic. A significant difference in NSI was observed between acute and chronic types (P < 0.05). Dynamic MRI was capable of classifying acute and chronic RA by measuring NSI 20?s after contrast medium injection. Dynamic MRI was therefore shown to be useful for assessing regional synovial inflammation.     

Contrast medium in power Doppler ultrasound for assessment of synovial vascularity: comparison with arthroscopy

OBJECTIVE: To evaluate the reliability of contrast-unenhanced power Doppler (CUPD) and contrast-enhanced power Doppler (CEPD) ultrasound (US) assessment of synovial vascularity of knee joint synovitis by prospective comparison with the "gold standard," arthroscopy. METHODS: A total of 18 knees of 17 patients with refractory rheumatoid and psoriatic knee joint synovitis were examined by US. Recognition of PD synovial vessel flow and its spatial arrangement in relation to the pannus/cartilage interface (P/CI) or fluid/synovium interface (F/SI) were studied by CUPD- and CEPD-US after a single intravenous bolus of galactosel palmitic acid (Levovist). Arthroscopy video recordings were reanalyzed by computer image analysis to assess synovial vascular marking. CUPD and CEPD flow signal scores were compared with each other and with corresponding vascular marking scores. Using villous vascular marking as reference, CUPD and CEPD sensitivity and specificity were measured. Interobserver variability was evaluated. RESULTS: Compared with the unenhanced PD method, contrast administration increased the PD flow signal score in 13/18 knees (72.2%), allowing increased detection of F/SI PD flow signal configuration (p < 0.018) and of the coexistence of P/CI and F/SI PD imaging (p < 0.0078). With arthroscopy as reference, contrast-enhanced PD was found to be more useful than the unenhanced method, showing more reproducible PD signal scores (p = 0.05 vs p = nonsignificant), as well as higher sensitivity (80% vs 30%), but lower specificity (62% vs 87%), in the recognition of increased vascularity of synovial villi. Interobserver agreement was 100%. CONCLUSION: The prospective comparison with arthroscopy showed the reliability of the CEPD method in synovial vessel recognition and its potential clinical usefulness in assessment of knee joint synovitis.     

Participation of substance P distribution in the cytokine production of rheumatoid synovium

Based on findings which suggested the involvement of the neuropeptide substance P in the pathogenesis of rheumatoid arthritis (RA), we investigated the mechanism of synovial pannus formation in RA, and examined the interaction between the cytokine production of synovial tissues and the concentration of substance P in the cartilage–pannus junction (CPJ). The CPJ and other peripheral synovial tissues were separately obtained from each part of the synovium from the knee joints of seven RA patients. The concentrations of substance P and the cytokines interleukin (IL)-1β and IL-6 in the CPJ and peripheral synovial tissues were determined by enzyme-linked immunosorbent assays. In addition, synovial cells were isolated from the CPJ and peripheral synovial tissues and treated with substance P or neurokinin-1 receptor antagonist to analyze the changes in cytokine production. The substance P levels were 211.2 and 50.5 pg/mg protein in the CPJ and the peripheral synovium, respectively. The IL-1β and IL-6 levels in the CPJ were 24.6 and 12.8 pg/mg protein, respectively. In the peripheral synovium, these levels were 4.3 and 2.5 pg/mg protein, respectively. In the CPJ, the IL-1β and IL-6 levels in tissue containing a high concentration of substance P (>200 pg/mg protein) were 39.4 and 21.6 pg/mg protein, respectively, and those in tissue containing a low concentration of substance P (≤200 pg/mg protein) were 11.6 and 5.1 pg/mg protein, respectively. Synovial cells from the CPJ produced higher levels of IL-1β and IL-6 than those from peripheral tissues. In addition, treatment of the cells with an NK-1 antagonist significantly reduced the production of these cytokines by the synovial cells. The theory that substance P plays a role in the pathogenesis of RA via the upregulation of cytokine production should be considered in further studies on the immunomodulatory properties of substance P in arthritis. Received: June 17, 1998 / Accepted: February 4, 2000     

Reactivity of monoclonal anti-type II collagen antibodies with cartilage and synovial tissue in rheumatoid arthritis and osteoarthritis

Monoclonal antibodies to 3 different epitopes on native type II collagen were used for immunohistochemical analysis of antigenic determinants that are exposed in the cartilage and synovial tissue obtained from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Two of the monoclonal antibodies reacted with cartilage from both OA and RA joints, but not with that from normal joints. The third monoclonal did not stain any of the cartilage sections. The 2 positive antibodies also reacted with cartilage fragments in the synovial tissue of both RA and OA joints, and in RA pannus tissue, the antibodies showed intracellular staining in many class II transplantation antigen-expressing synovial cells lying close to the damaged cartilage.     

Efficacy of arthroscopic synovectomy for the effect attenuation cases of infliximab in rheumatoid arthritis

To investigate whether arthroscopic synovectomy is effective for nonresponders to infliximab, anti-tumor necrosis factor-α antibody, for the treatment of rheumatoid arthritis (RA), we assessed seven patients including ten arthroscopic synovectomies in knee joint, in shoulder joint, and in ankle joints. We compared C-reactive protein (CRP) and DAS28 (ESR) before and after surgery at 6 and 50 weeks. After arthroscopic synovectomy, we continued the infliximab treatment with methotrexate in a routine manner. We detected synovium proliferation with vascular increase in patellofemoral joint and around the meniscus and femoral and tibial side of the anterior cruciate ligament in the knee joints. We also found synovial proliferation in rotator interval in the glenohumeral joint and fatty changing in subacromial bursa in the shoulder. In the ankle joint, we found synovial proliferation with white meniscoid between tibiofibular joint to develop impingement. Serum CRP was improved from 3.45±0.4 to 1.12±0.2 at 6 weeks to 1.22±0.4 at 50 weeks after arthroscopic synovectomy. There is no severe side effect of arthroscopic synovectomy during infliximab treatment; however, one patient had slight rash that was improved. DAS28 was improved from 5.58±0.23 to 3.87±0.47 at 6 weeks to 2.58±1.49 at 50 weeks after arthroscopic synovectomy. It is possible that arthroscopic synovectomy can be one of the effective methods to continue with the infliximab treatment when its efficacy decreased or in the nonresponders of infliximab for RA patients.     

Intra-articular methotrexate versus corticosteroid injections in medium-sized joints of rheumatoid arthritis patients—an intervention study

The effects of intra-articular methotrexate (I/A MTX) in knee synovitis in rheumatoid arthritis have been previously evaluated. I/A MTX has not been studied in other joints. Ultrasonography (US) has been little studied in monitoring the effect of I/A MTX. The aim of the study is to test the efficacy of I/A MTX in suppression of persistent synovitis in medium-sized joints (ankle, wrist, and elbow) in rheumatoid arthritis patients. Patients were divided into two groups: group 1 (methotrexate group): 56 patients in which 84 joints (32 ankles, 28 wrists, and 24 elbows) were injected intra-articularly by 10 mg of methotrexate in the targeted joint on a weekly basis for 8 weeks and group 2 (steroid group): 44 patients in which 70 joints (26 ankles, 24 wrists, and 20 elbows) were injected once by Triamcinolone acetonide 40 mg. Clinical, ultrasonographic, and power Doppler US (PDUS) evaluation was done before the first injection (W0), after 2 months (W8), and after 5 months (W20). Synovial thickness and the intra-articular power Doppler signal were graded on a semiquantitative scale from 0 to 3 during the US examination. Clinical parameters improved significantly in both groups between baselines and 2 months. In both groups, gray-scale US and power Doppler US showed that synovial thickness and intra-articular power signals were reduced significantly between W0 and W8. The improvement of clinical parameters continued in the methotrexate group up to W20, but in the corticosteroid group, clinical parameters at W20 were similar to clinical parameters at W0. In the methotrexate group, there was an insignificant increase in synovial thickness between W8 and W20 while there was a significant increase in power Doppler signals between W8 and W20, p < 0.05. In the corticosteroid group, there was a significant increase in both synovial thickening and power Doppler signals between W8 and W20, p < 0.001. In the MTX group, all patients at week 0 showed that the Doppler signal in grades 2 and 3 is 100%; at 8 weeks, most of the patients showed that the power Doppler in grade 0 is 76%; and at week 20, most of the patients showed that the power Doppler signal in grade 0 is 28% and in grade 1 is 47%, while in grades 2 and 3 is 23.6%, so there is an improvement compared to the baseline of treatment. Repeated I/A MTX resulted in a decrease in the degree of synovitis of medium-sized joints in RA patients both clinically and by power Doppler US.     

Ultrasonographic evaluation of synovial effusion and synovial proliferation pattern in the knee joints of patients with rheumatoid arthritis

In the present study, 49 knee joints of 26 patients with rheumatoid arthritis and 17 knee joints of 17 healthy subjects were ultrasonographically examined. Lateral, superior, and medial aspects of the patella were scanned using an ultrasonograph with a 7.5-MHz annular array transducer to evaluate the thickness of synovial effusion and the synovial proliferation pattern. The overall mean thickness of synovial effusion (mean of all three sites) in the knee joints was 4.9 ± 3.4 mm for rheumatoid arthritis patients and 1.4 ± 0.5 mm for healthy subjects. In rheumatoid arthritis patients, the mean thickness of synovial effusion at the superior aspect of the patella (6.5 ± 4.1 mm) was significantly greater than that at the lateral aspect (4.5 ± 4.8 mm) (P < 0.05) and the medial aspect (4.0 ± 3.1 mm) (P < 0.01). Patients with the villonodular pattern of synovial proliferation had a shorter duration of disease than those with uniform thickening or an overlapping pattern. Received: May 1, 2001 / Accepted: August 6, 2001